Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis
This study will examine the safety of Zenapax (daclizumab) in patients with multiple sclerosis (MS). MS is thought to be caused by an over-reactive immune response. T-lymphocytes (cells of the immune system), are thought to damage myelin, a substance that covers the nerve and parts of the spinal cord and is damaged in patients with MS. Interleukin-2 is a natural substance in the body that is necessary for the growth of T-lymphocytes. Zenapax is a genetically engineered antibody that blocks the activity of interleukin-2 and thus interferes with the growth of lymphocytes. Therefore, Zenapax may prevent some of the damage to myelin that occurs in multiple sclerosis.
Patients between 18 and 65 years of age with relapsing remitting MS may be eligible for this study. Patients with secondary-progressive or primary progressive MS may not participate. Candidates will be screened with a complete neurological and medical evaluation and review of medical records.
Participants will undergo the following tests and procedures:
- Baseline evaluation: Participants have four magnetic resonance imaging (MRI) scans over a 3-month period to assess disease activity. For the MRI scans, the patient lies on a table that slides into the scanner - a narrow metal cylinder with a strong magnetic field. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Only patients with activity at or above a certain level are eligible to continue with the treatment phase of the study.
- Zenapax treatment: Patients receive intravenous (through a vein) infusions of Zenapax. The first two infusions are 2 weeks apart, followed by 13 monthly infusions.
- MRI scans: Patients undergo MRI scanning before every infusion to evaluate disease activity and identify new brain lesions.
- Blood and urine tests: Blood and urine samples are collected at each clinic visit for routine laboratory evaluations, immunologic study, and genetic testing to determine a predisposition for responding to Zenapax treatment.
- Lumbar puncture (spinal tap): This procedure will be done during the last month before starting treatment and during the seventh month of treatment to examine immune changes that occur in the cerebrospinal fluid (CSF), which circulates through and surrounds the brain and spinal cord. A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle.
- Skin test: A needle is placed just under the skin is done to assess the patient's immune status to common antigens such as tetanus, mumps and candida.
- Lymphocytopheresis: Lymphocytes are collected three times - once during the last month of baseline before starting treatment, once during the fifth month of treatment, and once during the last month of treatment - for immunologic study. Blood is collected through a needle in an arm vein in a similar way to donating blood. The blood flows from the vein through a catheter (plastic tube) into a machine that separates it into its components by centrifugation (spinning). The lymphocytes are removed and the rest of the blood (red cells, plasma and platelets) is returned to the body, either through the same needle or through another needle in the other arm.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Zenapax (Daclizumab) Admin to Pts With Multiple Sclerosis (ZAP MS): Effect of Intravenously Admin Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (Daclizumab) on Inflammatory Activity in the Central Nervous System|
- Reduction in mean number of new gaolinium-enhancing lesions in the treatment phase (Weeks 18 to 30) versus baseline (Weeks -12 to 0). [ Designated as safety issue: Yes ]
- Mean change in the MS functional composite from completion of treatment. Reduction of mean number of new gaolinium-enhancing lesions at the completion of treatment. Mean change in Multiple Sclerosis Quality of Life Inventory from completion of t...
|Study Start Date:||October 2003|
|Study Completion Date:||August 2011|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease leading to central nervous system (CNS) inflammation, demyelination, axonal loss, and leads to substantial disability in young adults. Existing approved treatments include interferon beta, glatiramer acetate and mitoxantrone. These therapies are only moderately effective in reducing disease activity.
The Neuroimmunology Branch (NIB) has during the last three years tested the tolerability and safety of monthly intravenously administered daclizumab (Zenapax(Registered Trademark)), a humanized monoclonal antibody against the IL-2 receptor alpha chain, in patients who receive interferon-beta, but responded incompletely to therapy with interferon-beta. Daclizumab has been well tolerated and inhibited inflammatory disease activity by almost 90%. Under an amendment of this protocol, it was demonstrated that the efficacy of daclizumab is maintained once interferon-beta therapy is discontinued.
In the current trial, we will test the efficacy of daclizumab alone in relapsing-remitting MS patients. This trial is a single-centre, open-label, baseline to treatment cross-over phase II trial. Daclizumab will be administered intravenously at 1mg/kg bodyweight. Contrast-enhancing MRI lesions will serve as the primary outcome measure in this phase II trial, and a number of clinical, MRI, and immunological parameters will be measured as secondary and tertiary outcomes. Daclizumab is a promising new immunomodulatory treatment for relapsing-remitting MS.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|